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Mediterranean Diet and Hepatocellular Carcinoma
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"Combining two large studies carried out in the Mediterranean region, we found that the degree of adherence to Mediterranean diet is significantly inversely related to HCC risk in a roughly monotonic way, so that the MDS ≥5 (score of adherence to the diet with 5 being just past midway & 9 the highest) was associated with an about 50% reduction in HCC incidence in comparison to MDS of 3 or less. We also found that there is evidence, albeit statistically non significant, of super additivity in the risk implications of joint chronic hepatitis B and/or C infection and poor adherence to Mediterranean diet.
Several studies have shown a beneficial role of the traditional Mediterranean diet on health and longevity [20, 26-29]. The Mediterranean pattern has also been inversely related to cancer overall [8, 9, 30, 31], as well as specific forms of cancer [32-40]. Up to now, however, no study has investigated the association between Mediterranean diet and liver cancer risk."

Article in Press
Mediterranean Diet and Hepatocellular Carcinoma
Jnl of Hepatology Article in Press Nov 2013
Federica Turati1, Dimitrios Trichopoulos2, Jerry Polesel3, Francesca Bravi1,4, Marta Rossi1,8, Renato Talamini3, Silvia Franceschi5, Maurizio Montella6, Antonia Trichopoulou7, Carlo La Vecchia1,8*, Pagona Lagiou2,7* * Carlo La Vecchia and Pagona Lagiou share senior co-authorship 1IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Dipartimento di Epidemiologia; Milan, Italy.
2Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. 3S.O.C. Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, IRCCS, Aviano (PN), Italy 4Struttura Complessa di Statistica Medica, Biometria e Bioinformatica. Fondazione IRCCS Istituto Nazionale Tumori, Milan; Italy 5International Agency for Research on Cancer, Lyon Cedex, France. 6Dipartimento di Epidemiologia, 'Fondazione G. Pascale', Istituto Nazionale Tumori, Naples, Italy. 7Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece. 8Department of Clinical Sciences and Community Health, University of Milan, Milan; Italy.
Background & aims

Hepatocellular carcinoma (HCC) has a very poor prognosis and any effort to identify additional risk factors, besides those already established, would be important for the prevention of the disease. Data on the role of diet on HCC risk are still controversial.
We have evaluated the association of adherence to the Mediterranean diet with HCC risk, as well as the interaction of this dietary pattern with chronic hepatitis infection, by combining two case-control studies undertaken in Italy and Greece, including overall 518 cases of HCC and 772 controls. Adherence to the traditional Mediterranean diet was assessed through the Mediterranean diet score (MDS), which ranges between 0 (lowest adherence) and 9 (highest adherence). Odds ratios (OR) for HCC were obtained through multiple logistic regression models, controlling for potentially confounding variables, including chronic infection with hepatitis B/C viruses.
Compared to MDS of 0-3, the ORs for HCC were 0.66 (95% confidence interval (CI), 0.41-1.04) for MDS equal to 4 and 0.51 (95% CI, 0.34-0.75) for MDS 5, with a significant trend (p<0.001). The detrimental effect of poor adherence to Mediterranean diet on HCC risk was disproportionally high among those chronically infected with hepatitis B and/or C viruses, with a suggestion of super-additivity additive interaction, albeit statistically non-significant.
Closer adherence to the Mediterranean diet appears to be protective against HCC. Our results also point to potential benefits from adhering to a Mediterranean dietary pattern for patients chronically infected with hepatitis viruses.
Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer. The predominant role of chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) in the aetiology of HCC is well documented [1]. Several other risk factors for HCC have been identified, including heavy alcohol intake, tobacco smoking, and obesity [2].
With the exception of aflatoxins, data on the role of diet on liver cancer are inconclusive. Some studies have shown a weak inverse association between fruit consumption and liver cancer risk, and a positive one with glycaemic load, but evidence is sparse and inconsistent [3, 4].
It has been reported that for certain diseases, notably coronary heart disease, no food, food group, or nutrient has been implicated as causal, but the evidence for a favorable role of the Mediterranean dietary pattern is convincing [5]. Data are much scantier on Mediterranean diet and cancer risk [6-9]. Because HCC is a disease with a very poor prognosis, with a 5-year survival rate of less than 10% [10], any effort to identify additional modifiable causes of liver cancer would be important in order to allow a more effective prevention of the disease.
We have therefore evaluated the association between the Mediterranean dietary pattern and liver cancer by combining two large case-control studies undertaken in Italy and Greece, two countries in which the traditional Mediterranean diet is still prevalent. Age-standardized mortality from primary liver cancer (mainly HCC) is around 3/100,000 population in these countries [11]. Thus, despite being more common than in most other high income countries, HCC is still a rare disease, with a lifelong cumulative incidence around 1% in the general population.
The Mediterranean diet
The Mediterranean diet score (MDS) is based on 9 dietary components typical of the traditional Mediterranean diet. For each study subject, a value of 0 or 1 was assigned to each component of the score as follows: for components frequently consumed in the traditional Mediterranean diet (i.e., vegetables, legumes, fruit and nuts, cereals, fish and seafood, as well a high ratio of monounsaturated to saturated lipids), participants whose consumption was above or equal to the component study- and sex-specific median, calculated among controls, were assigned a value of 1, and 0 otherwise; for components less frequently consumed in the traditional Mediterranean diet (dairy, as well as meat and meat products), participants whose consumption was above or equal to the component study- and sex-specific median among controls were assigned a value of 0, and 1 otherwise. For alcohol, a value of 1 was assigned to moderate drinkers (that is, men who do drink but no more than 2 glasses per day, and women who do drink but no more than 1 glass every other day) and a value of 0 to those with consumption above these values, as well as to nondrinkers. The MDS was then calculated by summing up the points for each of the nine components. Thus, the score ranged between 0 (lowest adherence) and 9 (highest adherence).
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